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Glucocorticoid receptor physiology

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Abstract

Glucocorticoid action in cells is mediated by a specific receptor protein, the glucocorticoid receptor (GR). GR is a member of a superfamily of ligand-inducible transcription factors that control a variety of physiological functions; such as, metabolism, development, and reproduction. Unliganded GR is predominantly localized within the cytoplasm but rapidly and efficiently translocates to the nucleus following hormone binding. This review will focus on the intracellular signaling pathway utilized by the GR including the mechanisms that control its intracellular trafficking, hormone binding and transcriptional regulation. Many receptor-interacting proteins are involved in distinct steps in GR signal transduction, each with a unique mechanism to regulate receptor action and providing potential drug targets for the manipulation of cellular responses to glucocorticoids.

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References

  1. Jensen EV. On the mechanism of estrogen action. Perspect Biol Med 1962;6:47–59.

    CAS  Google Scholar 

  2. Ward E, Slocumb CH, Polley HF, Kendall EC, Hench PS. Clinical effects of cortisone administered orally to 100 patients with rheumatoid arthritis. Ann Rheum Dis 1951;10:477–84.

    PubMed  CAS  Google Scholar 

  3. Munck A, Brinck-Johnsen T. Specific and nonspecific physicochemical interactions of glucocorticoids and related steroids with rat thymus cells in vitro. J Biol Chem 1968;243:5556–65.

    PubMed  CAS  Google Scholar 

  4. Hollenberg SM, Weinberger C, Ong ES, Cerelli G, Oro A, Lebo R, Thompson EB, Rosenfeld MG, Evans RM. Primary structure and expression of a functional human glucocorticoid receptor cDNA. Nature 1985;318:635–41.

    Article  PubMed  CAS  Google Scholar 

  5. McEwan IJ, Wright AP, Dahlman-Wright K, Carlstedt-Duke J, Gustafsson JA. Direct interaction of the tau 1 transactivation domain of the human glucocorticoid receptor with the basal transcriptional machinery. Mol Cell Biol 1993;13:399–407.

    PubMed  CAS  Google Scholar 

  6. Dahlman-Wright K, Baumann H, McEwan IJ, Almlof T, Wright AP, Gustafsson JA, Hard T. Structural characterization of a minimal functional transactivation domain from the human glucocorticoid receptor. Proc Natl Acad Sci U S A 1995;92:1699–703.

    Article  PubMed  CAS  Google Scholar 

  7. Freedman LP, Luisi BF. On the mechanism of DNA binding by nuclear hormone receptors: a structural and functional perspective. J Cell Biochem 1993;51:140–150.

    Article  PubMed  CAS  Google Scholar 

  8. Tsai MJ, O'Malley B. Molecular mechanisms of action of steroid/thyroid receptor superfamily members. Annu Rev Biochem 1994;63:451–86.

    Article  PubMed  CAS  Google Scholar 

  9. Savory JG, Hsu B, Laquian IR, Giffin W, Reich T, Hache RJ, Lefebvre YA. Discrimination between NL1- and NL2-mediated nuclear localization of the glucocorticoid receptor. Mol Cell Biol 1999;19:1025–37.

    PubMed  CAS  Google Scholar 

  10. MacGregor J, Jordan V. Basic guide to the mechanisms of antiestrogen action. Pharmacol Rev 1998;50:151–96.

    PubMed  CAS  Google Scholar 

  11. Beato M, Klug J. Steroid hormone receptors: an update.. Hum Reprod Update 2000;6:225–36.

    Article  PubMed  CAS  Google Scholar 

  12. Galigniana MD, Scruggs JL, Herrington J, Welsh MJ, Carter-Su C, Housley PR, Pratt WB. Heat shock protein 90-dependent (geldanamycin-inhibited) movement of the glucocorticoid receptor through the cytoplasm to the nucleus requires intact cytoskeleton. Mol Endocrinol 1998;12:1903–13.

    Article  PubMed  CAS  Google Scholar 

  13. Bamberger C, Schulte H, Chrousos G. Molecular determinants of glucocorticoid receptor function and tissue sensitivity to glucocorticoids. Endocr Rev 1996;17:245–61.

    Article  PubMed  CAS  Google Scholar 

  14. Newton R. Molecular mechanisms of glucocorticoid action: what is important. Thorax 2000;55:603–13.

    Article  PubMed  CAS  Google Scholar 

  15. Cole T, Blendy J, Monaghan A, Schmid W, Aguzzi A, Schutz G. Molecular genetic analysis of glucocorticoid signaling during mouse development. Steroids 1995;60:93–6.

    Article  PubMed  CAS  Google Scholar 

  16. Beato M. Gene regulation by steroid hormones. Cell 1989;56:335–44.

    Article  PubMed  CAS  Google Scholar 

  17. Drouin J, Sun YL, Chamberland M, Gauthier Y, De Lean A, Nemer M, Schmidt TJ. Novel glucocorticoid receptor complex with DNA element of the hormone-repressed POMC gene. Embo J 1993;12:145–56.

    PubMed  CAS  Google Scholar 

  18. Adcock I, Ito K, Barnes P. Glucocorticoids: effects on gene transcription. Proc Am Thorac Soc 2004;1:247–54.

    Article  PubMed  CAS  Google Scholar 

  19. Yang-Yen H-F, Chambard J-C, Sun Y-L, Smeal T, Schmidt TJ, Drouin J, Karin M. Transcriptional interference between c-Jun and the glucocorticoid receptor: mutual inhibition of DNA-binding due to direct protein–protein interaction. Cell 1990;62:1205–15.

    Article  PubMed  CAS  Google Scholar 

  20. Hayashi R, Wada H, Ito K, Adcock I. Effects of glucocorticoids on gene transcription. Eur J Pharmacol 2004;500:51–62.

    Article  PubMed  CAS  Google Scholar 

  21. Wintermantel T, Berger S, Greiner E, Schutz G. Genetic dissection of corticosteroid receptor function in mice. Horm Metab Res 2004;36:387–91.

    Article  PubMed  CAS  Google Scholar 

  22. Reichardt H, Tuckermann J, Gottlicher M, Vujic M, Weih F, Angel P, Herrlich P, Schutz G. Repression of inflammatory responses in the absence of DNA binding by the glucocorticoid receptor. EMBO J 2001;20:7168–73.

    Article  PubMed  CAS  Google Scholar 

  23. Reichardt HM, Kaestner KH, Tuckermann J, Kretz O, Wessely O, Bock R, Gass P, Schmid W, Herrlich P, Angel P, Schutz G. DNA binding of the glucocorticoid receptor is not essential for survival. Cell 1998;93:531–41.

    Article  PubMed  CAS  Google Scholar 

  24. Simons SJ, Sistare F, Chakraborti P. Steroid binding activity is retained in a 16-kDa fragment of the steroid binding domain of rat glucocorticoid receptors. J Biol Chem 1989;264:14493–7.

    PubMed  CAS  Google Scholar 

  25. Bresnick EH, Dalman FC, Sanchez ER, Pratt WB. Evidence that the 90-kDa heat shock protein is necessary for the steroid binding conformation of the L cell glucocorticoid receptor. J Biol Chem 1989;264:4992–7.

    PubMed  CAS  Google Scholar 

  26. Czar MJ, Galigniana MD, Silverstein AM, Pratt WB. Geldanamycin, a heat shock protein 90-binding benzoquinone ansamycin, inhibits steroid-dependent translocation of the glucocorticoid receptor from the cytoplasm to the nucleus. Biochemistry 1997;36:7776–85.

    Article  PubMed  CAS  Google Scholar 

  27. Cheung J, Smith D. Molecular chaperone interactions with steroid receptors: an update. Mol Endocrinol 2000;14:939–46.

    Article  PubMed  CAS  Google Scholar 

  28. Johnson JL, Toft DO. Binding of p23 and hsp90 during assembly with the progesterone receptor. Mol Endocrinol 1995;9:670–768.

    Article  PubMed  CAS  Google Scholar 

  29. Davies T, Ning Y, Sanchez E. A new first step in activation of steroid receptors: hormone-induced switching of FKBP51 and FKBP52 immunophilins. J Biol Chem 2002;277:4597–600.

    Article  PubMed  CAS  Google Scholar 

  30. Pratt W, Toft D. Steroid receptor interactions with heat shock protein and immunophilin chaperones. Endocr Rev 1997;18:306–60.

    Article  PubMed  CAS  Google Scholar 

  31. Smith D. Tetratricopeptide repeat cochaperones in steroid receptor complexes. Cell Stress Chaperones 2004;9:109–21.

    Article  PubMed  CAS  Google Scholar 

  32. Glass CK, Rosenfeld MG. The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev 2000;14:121–41.

    PubMed  CAS  Google Scholar 

  33. Holaska JM, Black BE, Love DC, Hanover JA, Leszyk J, Paschal BM. Calreticulin is a receptor for nuclear export. J Cell Biol 2001;152:127–40.

    Article  PubMed  CAS  Google Scholar 

  34. Freedman ND, Yamamoto KR. Importin 7 and importin alpha/importin beta are nuclear import receptors for the glucocorticoid receptor. Mol Biol Cell 2004;15:2276–86.

    Article  PubMed  CAS  Google Scholar 

  35. Schaaf MJ, Cidlowski JA. Molecular mechanisms of glucocorticoid action and resistance. J Steroid Biochem Mol Biol 2002;83:37–48.

    Article  PubMed  CAS  Google Scholar 

  36. Irusen E, Matthews JG, Takahashi A, Barnes PJ, Chung KF, Adcock IM. p38 Mitogen-activated protein kinase-induced glucocorticoid receptor phosphorylation reduces its activity: role in steroid-insensitive asthma. J Allergy Clin Immunol 2002;109:649–57.

    Article  PubMed  CAS  Google Scholar 

  37. Yamamoto KR, Stampfer MR, Tomkins GM. Receptors from glucocorticoid-sensitive lymphoma cells and two classes of insensitive clones: physical and DNA-binding properties. Proc Natl Acad Sci U S A 1974;71:3901–5.

    Article  PubMed  CAS  Google Scholar 

  38. Itoh M, Adachi M, Yasui H, Takekawa M, Tanaka H, Imai K. Nuclear export of glucocorticoid receptor is enhanced by c-Jun N-terminal kinase-mediated phosphorylation. Mol Endocrinol 2002;16:2382–92.

    Article  PubMed  CAS  Google Scholar 

  39. Lee H, Bai W. Regulation of estrogen receptor nuclear export by ligand-induced and p38-mediated receptor phosphorylation. Mol Cell Biol 2002;22:5835–45.

    Article  PubMed  CAS  Google Scholar 

  40. Holaska JM, Black BE, Rastinejad F, Paschal BM. Ca2+-dependent nuclear export mediated by calreticulin. Mol Cell Biol 2002;22:6286–97.

    Article  PubMed  CAS  Google Scholar 

  41. Liu J, DeFranco DB. Protracted nuclear export of glucocorticoid receptor limits its turnover and does not require the exportin 1/CRM1-directed nuclear export pathway. Mol Endocrinol 2000;14:40–51.

    Article  PubMed  Google Scholar 

  42. Sikorski RS, Boguski MS, Goebl M, Hieter P. A repeating amino acid motif in CDC23 defines a family of proteins and a new relationship among genes required for mitosis and RNA synthesis. Cell 1990;60:307–17.

    Article  PubMed  CAS  Google Scholar 

  43. Blatch G, Lassle M. The tetratricopeptide repeat: a structural motif mediating protein–protein interactions. Bioessays 1999;21:932–9.

    Article  PubMed  CAS  Google Scholar 

  44. Nakao K, Myers JE, Faber LE. Development of a monoclonal antibody to the rabbit 8.5S uterin progestin receptor. Can J Biochem Cell Biol 1984;63:33–40.

    Article  Google Scholar 

  45. Borel J. Comparative study of in vitro and in vivo drug effects on cell-mediated cytotoxicity. Immunology 1976;31:631–41.

    PubMed  CAS  Google Scholar 

  46. Fung J, Thomson A, Pinna A, Selby R, Starzl T. State of immunosuppressive agents in organ transplantation. Transplant Proc 1992;24:2372–4.

    PubMed  CAS  Google Scholar 

  47. Liu J, Albers M, Wandless T, Luan S, Alberg D, Belshaw P, Cohen P, MacKintosh C, Klee C, Schreiber S. Inhibition of T cell signaling by immunophilin-ligand complexes correlates with loss of calcineurin phosphatase activity. Biochemistry 1992;31:3896–901.

    Article  PubMed  CAS  Google Scholar 

  48. Gkika D, Topala C, Hoenderop J, Bindels R. The immunophilin FKBP52 inhibits the activity of the epithelial Ca2+ channel TRPV5. Am J Physiol Renal Physiol 2006;290:F1253–9.

    Article  PubMed  CAS  Google Scholar 

  49. McCaffrey P, Luo C, Kerppola T, Jain J, Badalian T, Ho A, Burgeon E, Lane W, Lambert J, Curran T, et al. Isolation of the cyclosporin-sensitive T cell transcription factor NFATp. Science 1993;262:750–4.

    Article  PubMed  CAS  Google Scholar 

  50. Scheufler C, Brinker A, Bourenkov G, Pegoraro S, Moroder L, Bartunik H, Hartl FU, Moarefi I. Structure of TPR domain-peptide complexes: critical elements in the assembly of the Hsp70–Hsp90 multichaperone machine. Cell 2000;101:199–210.

    Article  PubMed  CAS  Google Scholar 

  51. Smith DF. Tetratricopeptide repeat cochaperones in steroid receptor complexes. Cell Stress Chaperones 2004;9:109–21.

    Article  PubMed  CAS  Google Scholar 

  52. Davies TH, Ning YM, Sanchez ER. Differential control of glucocorticoid receptor hormone-binding function by tetratricopeptide repeat (TPR) proteins and the immunosuppressive ligand FK506. Biochemistry 2005;44:2030–8.

    Article  PubMed  CAS  Google Scholar 

  53. Davies T, Sanchez E. FKBP52. Int J Biochem Cell Biol 2005;37:42–7.

    Article  PubMed  CAS  Google Scholar 

  54. Silverstein AM, Galigniana MD, Kanelakis KC, Radanyi C, Renoir JM, Pratt WB. Different regions of the immunophilin FKBP52 determine its association with the glucocorticoid receptor, hsp90, and cytoplasmic dynein. J Biol Chem 1999;274:36980–6.

    Article  PubMed  CAS  Google Scholar 

  55. Galigniana M, Radanyi C, Renoir J, Housley P, Pratt W. Evidence that the peptidylprolyl isomerase domain of the hsp90-binding immunophilin FKBP52 is involved in both dynein interaction and glucocorticoid receptor movement to the nucleus. J Biol Chem 2001;276:14884–9.

    Article  PubMed  CAS  Google Scholar 

  56. Chrousos G, Renquist D, Brandon D, Eil C, Pugeat M, Vigersky R, Cutler GJ, Loriaux D, Lipsett M. Glucocorticoid hormone resistance during primate evolution: receptor-mediated mechanisms. Proc Natl Acad Sci U S A 1982;79:2036–40.

    Article  PubMed  CAS  Google Scholar 

  57. Her S, Patel P, Schatzberg A, Lyons D. Mutations in squirrel monkey glucocorticoid receptor impair nuclear translocation. J Steroid Biochem Mol Biol 2005;94:319–26.

    Article  PubMed  CAS  Google Scholar 

  58. Westberry J, Sadosky P, Hubler T, Gross K, Scammell J. Glucocorticoid resistance in squirrel monkeys results from a combination of a transcriptionally incompetent glucocorticoid receptor and overexpression of the glucocorticoid receptor co-chaperone FKBP51. J Steroid Biochem Mol Biol 2006;100:34–41.

    Article  PubMed  CAS  Google Scholar 

  59. Reynolds PD, Ruan Y, Smith DF, Scammell JG. Glucocorticoid resistance in the squirrel monkey is associated with overexpression of the immunophilin FKBP51. J Clin Endocrinol Metab 1999;84:663–9.

    Article  PubMed  CAS  Google Scholar 

  60. Onate SA, Tsai SY, Tsai MJ, O'Malley BW. Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science 1995;270:1354–7.

    Article  PubMed  CAS  Google Scholar 

  61. McKenna NJ, Lanz RB, O'Malley BW. Nuclear receptor coregulators: cellular and molecular biology. Endocr Rev 1999;20:321–44.

    Article  PubMed  CAS  Google Scholar 

  62. Bannister AJ, Kouzarides T. The CBP co-activator is a histone acetyltransferase. Nature 1996;384:641–3.

    Article  PubMed  CAS  Google Scholar 

  63. Ogryzko VV, Schiltz RL, Russanova V, Howard BH, Nakatani Y. The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell 1996;87:953–9.

    Article  PubMed  CAS  Google Scholar 

  64. Spencer TE, Jenster G, Burcin MM, Allis CD, Zhou J, Mizzen CA, McKenna NJ, Onate SA, Tsai SY, Tsai MJ, O'Malley BW. Steroid receptor coactivator-1 is a histone acetyltransferase. Nature 1997;389:194–8.

    Article  PubMed  CAS  Google Scholar 

  65. Swope DL, Mueller CL, Chrivia JC. CREB-binding protein activates transcription through multiple domains. J Biol Chem 1996;271:28138–45.

    Article  PubMed  CAS  Google Scholar 

  66. Darimont BD, Wagner RL, Apriletti JW, Stallcup MR, Kushner PJ, Baxter JD, Fletterick RJ, Yamamoto KR. Structure and specificity of nuclear receptor–coactivator interactions. Genes Dev 1998;12:3343–56.

    PubMed  CAS  Google Scholar 

  67. Heery DM, Kalkhoven E, Hoare S, Parker MG. A signature motif in transcriptional co-activators mediates binding to nuclear receptors. Nature 1997;387:733–6.

    Article  PubMed  CAS  Google Scholar 

  68. Xu J, Liao L, Ning G, Yoshida-Komiya H, Deng C, O'Malley BW. The steroid receptor coactivator SRC-3 (p/CIP/RAC3/AIB1/ACTR/TRAM-1) is required for normal growth, puberty, female reproductive function, and mammary gland development. Proc Natl Acad Sci U S A 2000;97:6379–84.

    Article  PubMed  CAS  Google Scholar 

  69. Gehin M, Mark M, Dennefeld C, Dierich A, Gronemeyer H, Chambon P. The function of TIF2/GRIP1 in mouse reproduction is distinct from those of SRC-1 and p/CIP. Mol Cell Biol 2002;22:5923–37.

    Article  PubMed  CAS  Google Scholar 

  70. Xu J, Qiu Y, DeMayo FJ, Tsai SY, Tsai MJ, O'Malley BW. Partial hormone resistance in mice with disruption of the steroid receptor coactivator-1 (SRC-1) gene. Science 1998;279:1922–5.

    Article  PubMed  CAS  Google Scholar 

  71. Miyamoto H, Yeh S, Wilding G, Chang C. Promotion of agonist activity of antiandrogens by the androgen receptor coactivator, ARA70, in human prostate cancer DU145 cells. Proc Natl Acad Sci U S A 1998;95:7379–84.

    Article  PubMed  CAS  Google Scholar 

  72. Fujimoto N, Yeh S, Kang HY, Inui S, Chang HC, Mizokami A, Chang C. Cloning and characterization of androgen receptor coactivator, ARA55, in human prostate. J Biol Chem 1999;274:8316–21.

    Article  PubMed  CAS  Google Scholar 

  73. Yang L, Guerrero J, Hong H, DeFranco DB, Stallcup MR. Interaction of the tau2 transcriptional activation domain of glucocorticoid receptor with a novel steroid receptor coactivator, Hic-5, which localizes to both focal adhesions and the nuclear matrix. Mol Biol Cell 2000;11:2007–18.

    PubMed  CAS  Google Scholar 

  74. Cunha GR, Lung B. The possible influence of temporal factors in androgenic responsiveness of urogenital tissue recombinants from wild-type and androgen-insensitive (Tfm) mice. J Exp Zool 1978;205:181–93.

    Article  PubMed  CAS  Google Scholar 

  75. Chen JD, Evans RM. A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature 1995;377:454–7.

    Article  PubMed  CAS  Google Scholar 

  76. Horlein AJ, Naar AM, Heinzel T, Torchia J, Gloss B, Kurokawa R, Ryan A, Kamei Y, Soderstrom M, Glass CK, et al. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature 1995;377:397–404.

    Article  PubMed  CAS  Google Scholar 

  77. Li X, Kimbrel EA, Kenan DJ, McDonnell DP. Direct interactions between corepressors and coactivators permit the integration of nuclear receptor-mediated repression and activation. Mol Endocrinol 2002;16:1482–91.

    Article  PubMed  CAS  Google Scholar 

  78. Wang Q, Blackford JA Jr., Song LN, Huang Y, Cho S, Simons SS Jr. Equilibrium interactions of corepressors and coactivators with agonist and antagonist complexes of glucocorticoid receptors. Mol Endocrinol 2004;18:1376–95.

    Article  PubMed  CAS  Google Scholar 

  79. Szapary D, Huang Y, Simons SS Jr. Opposing effects of corepressor and coactivators in determining the dose–response curve of agonists, and residual agonist activity of antagonists, for glucocorticoid receptor-regulated gene expression. Mol Endocrinol 1999;13:2108–21.

    Article  PubMed  CAS  Google Scholar 

  80. Perissi V, Aggarwal A, Glass CK, Rose DW, Rosenfeld MG. A corepressor/coactivator exchange complex required for transcriptional activation by nuclear receptors and other regulated transcription factors. Cell 2004;116:511–26.

    Article  PubMed  CAS  Google Scholar 

  81. Li J, Wang J, Nawaz Z, Liu JM, Qin J, Wong J. Both corepressor proteins SMRT and N-CoR exist in large protein complexes containing HDAC3. Embo J 2000;19:4342–50.

    Article  PubMed  CAS  Google Scholar 

  82. Bellingham DL, Sar M, Cidlowski JA. Ligand-dependent down-regulation of stably transfected human glucocorticoid receptors is associated with the loss of functional glucocorticoid responsiveness. Mol Endocrinol 1992;6:2090–102.

    Article  PubMed  CAS  Google Scholar 

  83. Ramdas J, Liu W, Harmon JM. Glucocorticoid-induced cell death requires autoinduction of glucocorticoid receptor expression in human leukemic T cells. Cancer Res 1999;59:1378–85.

    PubMed  CAS  Google Scholar 

  84. Oakley RH, Cidlowski JA. Homologous down regulation of the glucocorticoid receptor: the molecular machinery. Crit Rev Eukaryot Gene Expr 1993;3:63–88.

    PubMed  CAS  Google Scholar 

  85. Wallace AD, Cidlowski JA. Proteasome-mediated glucocorticoid receptor degradation restricts transcriptional signaling by glucocorticoids. J Biol Chem 2001;276:42714–21.

    Article  PubMed  CAS  Google Scholar 

  86. Voges D, Zwickl P, Baumeister W. The 26S proteasome: a molecular machine designed for controlled proteolysis. Annu Rev Biochem 1999;68:1015–68.

    Article  PubMed  CAS  Google Scholar 

  87. Ciechanover A, Orian A, Schwartz AL. Ubiquitin-mediated proteolysis: biological regulation via destruction. Bioessays 2000;22:442–51.

    Article  PubMed  CAS  Google Scholar 

  88. Sengupta S, Wasylyk B. Ligand-dependent interaction of the glucocorticoid receptor with p53 enhances their degradation by Hdm2. Genes Dev 2001;15:2367–80.

    Article  PubMed  CAS  Google Scholar 

  89. Kinyamu HK, Archer TK. Estrogen receptor-dependent proteasomal degradation of the glucocorticoid receptor is coupled to an increase in mdm2 protein expression. Mol Cell Biol 2003;23:5867–81.

    Article  PubMed  CAS  Google Scholar 

  90. Connell P, Ballinger CA, Jiang J, Wu Y, Thompson LJ, Hohfeld J, Patterson C. The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins. Nat Cell Biol 2001;3:93–6.

    Article  PubMed  CAS  Google Scholar 

  91. Wang X, DeFranco DB. Alternative effects of the ubiquitin-proteasome pathway on glucocorticoid receptor down-regulation and transactivation are mediated by CHIP, an E3 ligase. Mol Endocrinol 2005;19:1474–82.

    Article  PubMed  CAS  Google Scholar 

  92. Wang X, Pongrac JL, DeFranco DB. Glucocorticoid receptors in hippocampal neurons that do not engage proteasomes escape from hormone-dependent down-regulation but maintain transactivation activity. Mol Endocrinol 2002;16:1987–98.

    Article  PubMed  CAS  Google Scholar 

  93. Ghosh B, Wood CR, Held GA, Abbott BD, Lau C. Glucocorticoid receptor regulation in the rat embryo: a potential site for developmental toxicity. Toxicol Appl Pharmacol 2000;164:221–9.

    Article  PubMed  CAS  Google Scholar 

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Heitzer, M.D., Wolf, I.M., Sanchez, E.R. et al. Glucocorticoid receptor physiology. Rev Endocr Metab Disord 8, 321–330 (2007). https://doi.org/10.1007/s11154-007-9059-8

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